Testicular pathophysiology contributes to the large majority of male infertility. Varicocele and testicular torsion are two pathologies whose mechanisms are not understood, but which are known to cause alterations in testicular blood flow. Experimental varicocele induces an increase in testicular blood flow; testicular torsion decreases blood flow. The experiments proposed in this application will address fundamental questions about the pathology and treatment of these lesions. The studies of experimental varicocele are those arising subsequent to previous work in this lab. We will examine the mechanisms by which unilateral varicocele induces a bilateral increase in testicular flood flow. We will also determine the specific effects of that increased blood flow on venous drainage pathways from the testis and on the availability of blood-borne molecules to the testicular interstitium. We will determine if site-directed hormonal therapy will prevent the varicocele-induced reduction in rat spermatogenesis. Testicular blood flow will also be studied in rats with graded testicular torsion, both during torsion and after torsion repair. Additionally, the effects of graded testicular torsion on ipsilateral Leydig cell function will be examined. Tissue ischemia is typically followed by reperfusion injury due to an increase in oxygen radical formation in the reperfused tissue and subsequent lipid peroxidation in cell membranes and mitochrondria. In this application, we propose to study the effects of oxygen radical scavengers on post-torsion testicular oxygen radical concentrations and to determine the effect of the scavengers on functional salvage of the torted testis. Thus, this application proposes studies of basic mechanisms of testicular pathophysiology as well as of potential treatments for the specific lesions studied.